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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina tsz Ki chan Dohyun Ahn Vladimir Kushnarev tsz Kiu Cheung Ho Ching chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng Leung chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Analysis of Neuroregenerative Effects By Gastrodia Elata Growing In Four Different Areas On Human Neuronal BE-2（C） Cells By Real Time Reverse Transcription·Polymerase Chain Reaction

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Analysis of Neuroregenerative Effects By Gastrodia Elata Gro...

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

第十四届全国中药和天然药物学术研讨会

作者： chan tsz chun Tang Yat Man Calvin Sin Kyle Hao Liu Michelle CH Ng Kei Fan Daniel Mok Foo Tim Chau Daniel Man Yuen Sze The Hong Kong Polytechnic University

＜正＞Introduction Neurodegenerative diseases have been a great concern of the *** elata can be a new way out for neurodegenerative diseases as it had neuroprotective and neuroregenerative *** project will analyze the...

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy Yuen-chun Teoh Samson Yun-Sang chan Ho-Man Tam Chi-Kwok chan Chi-Fai Ng Peter Ka-Fung Chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration

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Chinese Journal of Integrative Medicine 2024年第1期30卷 52-61页

作者： ZHOU Qi-chun XIAO Shi-lin LIN Ru-kun LI chan CHEN Zhi-jie CHEN Yi-fei LUO Chao-hua MO Zhi-xian LIN Ying-bo School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Clinical and Basic Research Team of TCM Prevention and Treatment of Non-Small Cell Lung Cancer the Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou(510120)China Department of Chinese Medicine Zhujiang Hospital Affiliated to Southern Medical UniversityGuangzhou(510282)China Department of Pharmacy Jiangmen Central HospitalJiangmen(529000)China

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata(PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 μg/m L, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction(qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with normal saline, positive control group(LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The cell apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein(P <0.05), up-regulation of Caspase-3 protein(P<0.05) and ERK1 mRNA(P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

关键词： polysaccharide of Alocasia cucullata tumor cells Bcl-2 Caspase-3 ERK1/2 Chinese medicine

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity:a territory-wide target trial emulation

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Family Medicine and Community Health 2024年第3期12卷 25-35页

作者： Cuiling Wei Vincent Ka chun Yan Camille Maringe Wenxin Tian Rachel Yui Ki Chu Wenlong Liu Boyan Liu Yuqi Hu Lingyue Zhou Celine Sze Ling Chui Xue Li Eric Yuk Fai Wan Ching Lung Cheung Esther Wai Yin chan William Chi Wai Wong Ian Chi Kei Wong Francisco tsz Tsun Lai Centre for Safe Medication Practice and Research Department of Pharmacology and PharmacyLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Health Services Research and Policy Faculty of Public Health and PolicyLondon School of Hygiene and Tropical MedicineLondonUK School of Nursing Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Laboratory of Data Discovery for Health(D24H) Hong KongHong Kong Advanced Data Analytics for Medical Science(ADAMS)Limited Hong KongHong Kong Department of Medicine School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Family Medicine and Primary Care School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongHong Kong Department of Pharmacy The University of Hong Kong-Shenzhen HospitalShenzhenPeople's Republic of China Aston Pharmacy School Aston UniversityBirminghamUK School of Pharmacy Macao University of Science and TechnologyTaipaMacao

Objectives Older individuals with multimorbidity are at an elevated risk of infection and complications from *** of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been *** study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with *** Retrospective cohort study emulating a randomised target trial using electronic health *** We used data from the Hospital Authority and the Department of Health in Hong Kong,which provided comprehensive electronic health records,COVID-19 confirmed case data,population-based vaccination records and other individual characteristics for the *** Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August *** Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure,compared to no outpatient *** outcome measures Primary outcome was all-cause mortality within one *** outcomes included mortality from respiratory,cardiovascular and cancer *** A total of 6183 eligible COVID-19 survivors were included in the *** all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group(17.1 deaths per 100 person-year)compared with non-visit group(42.8 deaths per 100 person-year).After adjustment,primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival(difference in 1-year survival:11.2%,95%CI 8.1%to 14.4%).We also observed significantly better survival from respiratory diseases in the general outpatient visit group(difference in 1-year survival:6.3%,95%CI 3.5%to 8.9%).In a sensitivity analysis for different grace period lengths

关键词： morbidity visit records

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai tsz chun Kwan John K.C.Li Karl C.K.chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben chung-Lap chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-chung Leung chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris chun-Yiu chan Qian Guo Jasper Fuk-Woo chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

Performance in the Fundamentals of Laparoscopic Surgery: Does it reflect global rating scales in the Objective Structured Assessment of Technical Skills in porcine laparoscopic surgery?

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Asian Journal of Urology 2024年第3期11卷 443-449页

作者： Ho Yee Tiong Wei Zheng So Jeremy Yuen-chun Teoh Shuji Isotani Gang Zhu Teng Aik Ong Eddie Shu-Yin chan Peggy Sau-Kwan Chu Kittinut Kijvikai Ming Liu Bannakji Lojanapiwat Michael Wong Anthony Chi-Fai Ng Yong Loo Lin School of Medicine Department of SurgeryNational University of SingaporeSingapore S.H.Ho Urology Centre Department of SurgeryThe Chinese University of Hong KongHong KongChina Department of Urology Juntendo University Graduate School of MedicineTokyoJapan Department of Urology National University HospitalSingapore Department of Urology Beijing United Family HospitalBeijingChina Department of Surgery University of Malaya Specialist CentreKuala LumpurMalaysia Division of Urology Department of SurgeryTuen Mun HospitalHong Kong Department of Urology Ramathibodi HospitalMahidol UniversitySalayaThailand Department of Urology Beijing HospitalBeijingChina Department of Urology Chiangmai Ram HospitalChiang MaiThailand International Urology Fertility&Gynaecology CentreSingapore

Objective:To correlate the utility of the Fundamentals of Laparoscopic Surgery(FLS)manual skills program with the Objective Structured Assessment of Technical Skills(OSATS)global rating scale in evaluating operative ***:The Asian Urological Surgery Training and Educational Group(AUSTEG)Laparoscopic Upper Tract Surgery Course implemented and validated the FLS program for its usage in laparoscopic surgical ***’basic laparoscopic skills were assessed using three different training models(peg transfer,precision cutting,and intra-corporeal suturing).They also performed live porcine laparoscopic surgery at the same *** surgery skills were assessed by blinded faculty using the OSATS rating ***:From March 2016 to March 2019,a total of 81 certified urologists participated in the course,with a median of 5 years of post-residency *** differences in task time did not reach statistical significance,those with more surgical experience were visibly faster at completing the peg transfer and intra-corporeal suturing FLS ***,they took longer to complete the precision cutting task than participants with less *** OSATS scores correlated weakly with all three FLS tasks(peg transfer time:r=0.331,r^(2)=0.110;precision cutting time:r=0.240,r^(2)=0.058;suturing with intracorporeal knot time:r=0.451,r^(2)=0.203).Conclusion:FLS task parameters did not correlate strongly with OSATS globing rating scale *** FLS task models demonstrated strong validity,it is important to assimilate the inconsistencies when benchmarking technical proficiency against real-life operative competence,as evaluated by FLS and OSATS,respectively.

关键词： TheFundamentalsof Laparoscopic Surgery The Objective Structured Assessment of Technical Skills Laparoscopic training Surgical education Surgical training Urological laparoscopic surgery

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提高肝癌转化治疗成功率的策略与挑战

中国实用外科杂志 2024年第9期44卷 1078-1080页

作者：陈智仁寇春伟纪任香港大学临床医学学院外科学系、香港玛丽医院肝脏移植科、肝胆胰外科中国香港香港大学深圳医院肝胆胰外科广东深圳518053

尽管根治性手术切除在肝癌治疗中效果显著,但仅约30%的病人有手术机会,而对于不可切除肝癌病人而言,预后仍不容乐观。近年来,包括免疫治疗在内的全身系统治疗方案在局部晚期肝癌的治疗中取得了重大进展。然而,这些治疗方案面临诸多挑战... 详细信息

尽管根治性手术切除在肝癌治疗中效果显著,但仅约30%的病人有手术机会,而对于不可切除肝癌病人而言,预后仍不容乐观。近年来,包括免疫治疗在内的全身系统治疗方案在局部晚期肝癌的治疗中取得了重大进展。然而,这些治疗方案面临诸多挑战,包括难以确定最佳治疗周期和停止治疗的具体时间点,以及较高的治疗相关不良事件发生率。仅约10%的病人能够通过全身系统治疗实现完全缓解。外科治疗的目标是通过转化治疗方案,将不可切除的肝癌病人转化为可切除,从而显著改善病人的预后。2022年,START-FIT临床试验推出了一种新型的多模式、序贯式治疗方案,结合了经动脉化疗栓塞、立体定向放疗和免疫疗法。该方案的初步结果显示,约40%的病人达到了完全缓解,另有12%的病人成功转化为手术治疗。这一进展为不可切除肝癌病人带来了新的希望,并为未来的治疗策略提供了重要的参考。

关键词：肝细胞癌转化治疗靶向治疗免疫治疗三联序贯式转化治疗